This phase II trial studies how well linsitinib works in treating younger and adult patients with gastrointestinal stromal tumors. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Patients will be stratified into pediatric and adult cohorts; patients in the pediatric cohort (age at diagnosis =< 18 years OR diagnosis of Carney Triad or Carney-Stratakis Diad (paraganglioma, pulmonary chondroma) must have received at least sunitinib and have had progression on or intolerance to progression on therapy; patients in the adult cohort (age at diagnosis > 18 years AND no diagnosis of diagnosis of Carney Triad or Carney-Stratakis Diad) have had progression on or intolerance to imatinib therapy as documented by treating physician

Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2

Patients must have measurable disease defined as lesions that can be measured in 2 dimensions by medical imaging techniques such as CT or magnetic resonance imaging (MRI); ascites, pleural fluid, and lesions seen on PET scan only are not considered measurable

QT interval corrected using Frederica formula (QTcF) interval average of < 450 msec at baseline using the Frederica formula (QTcF)

No concomitant drugs that prolong the QTc interval

No significant cardiac disease

Fasting blood glucose < 150 mg/dL at baseline

Hemoglobin A1C (HbA1c) < 7% at screening

Patients or their legal representative must be able to read, understand and provide written informed consent to participate in the trial

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 7days prior to registration

Patients with diabetes mellitus should have controlled disease on oral medications, defined as: no diabetic ketoacidosis (hyperglycemia, ketonuria, pH < 7.3 and bicarbonate < 15mEq/L) at the time of enrollment or within 30 days prior to enrollment and; no change in oral medications greater than 10% within 30 days prior to enrollment

Patient must be able to swallow to participate in the study

Signed informed consent

Exclusion Criteria:

Time elapsed from previous therapy must be >= 3 weeks except for prior tyrosine kinase inhibitor therapy which can be >= 7 days; patients must be recovered from the effects of any prior surgery, radiotherapy or systemic therapy

Patients who are receiving any other investigational agents or other anti-cancer therapies other than those administered in this study during protocol treatment

Patients with diabetes mellitus requiring insulin for control of their diabetes

Patients with a history of liver cirrhosis

Patients with known brain metastases should be excluded from this clinical trial

History of allergic reactions attributed to compounds of similar chemical or biologic composition to linsitinib (OSI-906)

While cytochrome P450 1A2 (CYP1A2) inhibitors/inducers are not specifically excluded, investigators should be aware that linsitinib (OSI 906) exposure may be altered by the concomitant administration of these drugs

While cytochrome P450 2C9 (CYP2C9) substrates are not specifically excluded, investigators should be aware that levels of drugs metabolized by CYP2C9 may be increased by the concomitant administration of linsitinib (OSI-906); caution should be used when administering CYP2C9 substrates to patients who are on study drug

Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine are prohibited; other less potent CYP1A2 inhibitors/inducers are not excluded

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with linsitinib (OSI-906)

Fertile men and women of childbearing potential not employing an effective method of birth control throughout the trial and for 3 months after last study drug administration in both sexes; women of childbearing potential must have a negative pregnancy test (serum or urine) within the 7 days prior to study drug administration

NOTE: Women of childbearing potential include both pre-menopausal women and women within the first 2 years of the onset of menopause

Use of drugs that have a known risk of causing Torsades de Pointes (TdP) are prohibited within 14 days prior to initiation of linsitinib (OSI-906)

Patients with a history of solid organ transplant are ineligible

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01560260